Immunohistochemical Analysis of Splenic B-cells in XLP P

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Abstract

Individuals with X-linked lymphoproliferative disease (XLP) display defects in B cell differentiation in vivo. Specifically, XLP patients do not generate a normal number of CD27 memory B cells, and those few that are present are IgM. Recent studies have suggested that IgMCD27 B cells are not true memory cells, but rather B cells that guard against T cell-independent pathogens. As a part of an effort to elucidate whether human XLP IgMCD27 B cells resemble normal memory B cells both morphologically and phenotypically, we have analyzed spleens from XLP patients using immunohistochemistry. Analysis of spleens from XLP patients revealed a paucity of germinal centers (GCs), and the rare GCs detected were poorly formed. Despite this, studies performed at the collaborating institution showed that Ig variable region genes expressed by XLP IgMCD27 B cells had undergone somatic hypermutation to the extent comparable to that of normal memory B cells. Additionally, IgMCD27 B cells exhibited functional characteristics of normal memory B cells, including the ability to secrete more Ig than naive B cells in response to both T cell-dependent and -independent stimuli. These findings reveal a differential requirement for the generation of IgM and Ig isotype-switched memory B cells, with the latter only being generated by fully formed GCs. Production of affinity-matured IgM by IgMCD27 B cells may protect against pathogens to which a normal immune response is elicited in XLP patients. One paper is published.